FDA – Health Law Advisorhttps://www.healthlawadvisor.com
Thought Leaders on Laws and Regulations Affecting Health Care and Life SciencesFri, 13 Sep 2019 18:37:35 +0000en-UShourly1https://wordpress.org/?v=4.9.11The FDA Looks Inward as It Tackles Interoperabilityhttps://www.healthlawadvisor.com/2019/09/13/the-fda-looks-inward-as-it-tackles-interoperability/
https://www.healthlawadvisor.com/2019/09/13/the-fda-looks-inward-as-it-tackles-interoperability/#respondFri, 13 Sep 2019 18:12:23 +0000https://www.healthlawadvisor.com/?p=2979Continue Reading…]]>Interoperability and patient access to data has been pushed to the forefront as a primary concern for the health industry. This is largely due to proposed rules published this spring by the Office of the National Coordinator for Health Information Technology (ONC) and the Center for Medicare and Medicaid Services (CMS) that seek to advance interoperability and support the access, exchange, and use of electronic health information. In August 2019, the ONC held its third annual National Coordinator for Health IT Interoperability Forum in Washington DC. The event brings together the Health IT technology community, developers, policymakers, and staff to promote the goal of interoperability. One of this year’s keynote speakers was the Food and Drug Administration (FDA)’s Principal Deputy Commissioner, Amy Abernethy, M.D. Ph.D.

Dr. Abernethy’s speech focused on improving the FDA’s competence as it steps into a more substantive role in promoting interoperability in health care. First, Dr. Abernethy highlighted the FDA’s need to improve its overall technical expertise in order to adequately engage with the industry and exchange data among the agency’s Centers. Furthermore, Dr. Abernethy emphasized the need for FDA to change the way it interacts with the technology community at large. Dr. Abernethy explained that, over the years, FDA has learned to work with drug and device industries, patient groups, and trade organizations, but lacks a similar effective line of communication with tech companies. Dr. Abernethy suggested that this may be due to the historical perception of tech firms as “vendors being told what to do rather than creating solutions with collaboration and guidance.” These efforts by FDA to enhance its capabilities to address increasingly prevalent interoperability concerns is a positive step for the agency, as technology is rapidly advancing and infiltrating the health care space. Such actions are in addition to FDA’s PrecisionFDA movement and the agency’s embrace of artificial intelligence in recent years. In her speech, Dr. Abernethy underscored that the FDA intends to learn from these initiatives in order to improve its capabilities in the future.

Dr. Abernethy ended her keynote by revealing FDA’s upcoming publication of an action plan to modernize the agency’s “approach to the use of technology for its regulatory mission, including the review of medical product applications.” The action plan is also rumored to include information on “uses of artificial intelligence, blockchain, and other technologies,” and promises stakeholder engagement. The action plan is scheduled to be released in the coming months. Stakeholders should monitor developments and evaluate how this update will change its engagement with the FDA. EBG will continue to monitor the progress of the FDA’s interoperability and modernization efforts.

]]>https://www.healthlawadvisor.com/2019/09/13/the-fda-looks-inward-as-it-tackles-interoperability/feed/0HHS and FDA Propose Action Plan for the Importation of Certain Foreign Drugs into the United Stateshttps://www.healthlawadvisor.com/2019/09/09/hhs-and-fda-propose-action-plan-for-the-importation-of-certain-foreign-drugs-into-the-united-states/
https://www.healthlawadvisor.com/2019/09/09/hhs-and-fda-propose-action-plan-for-the-importation-of-certain-foreign-drugs-into-the-united-states/#respondMon, 09 Sep 2019 19:32:54 +0000https://www.healthlawadvisor.com/?p=2972Continue Reading…]]>In an effort to address the challenge of increasing drug prices for patients and families, the U.S. Food and Drug Administration (“FDA”) and the U.S. Department of Health and Human Services (“HHS”) recently outlined a proposal for facilitating the importation of pharmaceuticals originally intended for foreign markets. The Safe Importation Action Plan (the “Action Plan”), jointly announced on July 31, 2019, describes two different potential pathways for importing certain drugs. The Action Plan offers only a limited overview of the proposed pathways and does not provide much detail on how these pathways would be implemented.

Below, we summarize the Action Plan’s two proposed pathways for the importation of certain drugs intended for foreign markets.

Pathway 1: Importation of Canadian Drugs by States, Wholesalers and Pharmacists Pursuant to Demonstration Projects

Under this pathway, HHS and FDA would publish a Notice of Proposed Rulemaking (“NPRM”) under the authority granted in Section 804 of the Federal Food, Drug and Cosmetic (“FDCA”). Section 804 of the FDCA authorizes the importation of certain prescription drugs from Canada upon the condition that the Secretary of HHS certifies that importation would “pose no additional risk” to U.S. consumers, and that such importation would “result in a significant reduction in the cost” of those prescription drugs. Since its enactment in 2003, no HHS Secretary has provided the certification required to import drugs under Section 804.

The NPRM would establish a framework allowing states, pharmacists, and wholesalers to import certain prescription drugs from Canada. Specifically, the drugs eligible for importation would need to: (a) be approved for sale in Canada; (b) contain essentially the same active pharmaceutical ingredient (“API”) used in the FDA-approved prescription drug (i.e., the same API manufacturing facility must produce the API used in both the Canadian-approved and FDA-approved drug and manufacture the API under FDA’s current Good Manufacturing Practices (“cGMPs”) listed in FDA’s drug approval); and (c) be labeled to indicate they were originally intended for distribution in Canada. Importers would be required to provide an attestation and supporting documentation regarding the authenticity and eligibility of the drug. The following categories of drugs are specifically excluded from eligibility under Pathway 1: controlled substances, biological products, infused drugs, intravenously injected drugs, drugs inhaled during surgery, certain parenteral drugs, and any drug subject to a Risk Evaluation and Mitigation Strategy.

To import products into the United States, states, wholesalers and pharmacists would need to submit a demonstration application to HHS explaining how they would comply with applicable safety, and other regulatory requirements (e.g., drug tracking and tracing from manufacturer to pharmacy, labeling, distributor registration, adverse event reporting, recalls, and cGMP compliance). Additionally, importers would be required to prove that that the importation of drugs under this pathway would result in a significant reduction in the cost of covered drugs to the American consumer. A demonstration application, if granted, would be time-limited and subject to revocation if the importer does not comply with specified requirements or a risk to public health or safety is identified.

Unlike Pathway 1, which is restricted to drugs approved by Health Canada, Pathway 2 would allow manufacturers to import versions of their FDA-approved drugs that are sold in foreign countries. To import drugs under this pathway, manufacturers (or their authorized representatives) would be required to establish that the version of the drug sold in a foreign country is the same as the U.S. version approved by FDA (e.g., through manufacturing records). If this condition is met, FDA would allow the drug to be labeled for sale in the United States and imported pursuant to section 801(d) of the FDCA under the existing approval for the U.S. version. Manufacturers who qualify to import drugs under this pathway would be permitted to market the imported drug under a different National Drug Code than the U.S. version. According to the Action Plan, this pathway “would highlight an opportunity for manufacturers to use importation to offer lower-cost versions of their drugs.” HHS is evaluating whether additional safeguards would be needed to ensure that the imported drug is a bona fide foreign version of an FDA-approved drug. FDA plans to publish a draft guidance document that will outline detailed recommendations on the requirements for importing products under Pathway 2.

Industry stakeholders have expressed concern that these new pathways would enable the entry of drugs outside the “gold standard” U.S. supply chain and thereby pose risk to U.S. patients. Concerns have also been raised internationally that the Action Plan may trigger drug shortages in Canada. It remains to be seen how HHS and FDA will address these concerns, as the Action Plan does not specify a timeline for publishing the proposed rule or the guidance document. Their publication will provide an opportunity for stakeholders to submit comments in response to the specific details of the proposed pathways. Stakeholders should continue to monitor any developments to the Action Plan and to submit comments on the proposals as they become available. Stakeholders should also evaluate the potential impact of these importation proposals on their current distribution and supply chains.

]]>https://www.healthlawadvisor.com/2019/09/09/hhs-and-fda-propose-action-plan-for-the-importation-of-certain-foreign-drugs-into-the-united-states/feed/0What’s New in E-Cigarette Regulation?https://www.healthlawadvisor.com/2019/08/14/whats-new-in-e-cigarette-regulation/
https://www.healthlawadvisor.com/2019/08/14/whats-new-in-e-cigarette-regulation/#respondWed, 14 Aug 2019 14:32:22 +0000https://www.healthlawadvisor.com/?p=2964Continue Reading…]]>There is little question that youth e-cigarette use has been on the rise. In 2018, an estimated 3.6 million kids reported “current use” of e-cigarettes (defined as use on at least one day in the past 30 days), up from just 220,000 kids reporting such use in 2011 (See National Youth Tobacco Survey findings). Although youth e-cigarette use raises public health concerns, there’s also a public health upside to e-cigarettes, as they have been shown to be an effective tool in helping current adult cigarette smokers kick the habit and are a safer option for current smokers than combustible tobacco products (e.g., cigarettes). Therefore, it seems that broad restrictions on everyone’s access to these products is probably not the solution here. So what is the answer? How do we keep e-cigarettes out of the hands of children, but maintain their availability for adult cigarette smokers? Let’s track what’s recently been done on the federal and state/local levels to address the issue.

On the federal level, per FDA’s May 2016 “Deeming Rule,” e-cigarettes became subject to FDA’s tobacco product authorities, including, most notably, the requirement that e-cigarettes obtain FDA premarket authorization. For most products, such authorization requires submission of a Premarket Tobacco Product Application (“PMTA”). In their PMTAs, e-cigarette manufacturers must demonstrate that their proposed e-cigarette product is “appropriate for the protection of the public health.” Although FDA released guidance in June 2019 related to the PMTA process, there is still a considerable lack of clarity with regard to how manufacturers can show this broad review standard is satisfied.

The deadline for PMTA submission was initially set for August 2018, but in 2017, FDA pushed back the deadline to August 2022, prompting a lawsuit against the Agency (AAP et al. v. FDA (S.D. MD)). In a July 2019 ruling, the federal judge in this case ordered FDA to impose a 10-month deadline for the submission of PMTAs. As FDA gears up to accommodate PMTA reviews under this accelerated time frame, the Agency noted that it will also continue utilizing other regulatory tools to combat youth e-cigarette use, including enforcement against retailers selling to minors and youth educational and advertising campaigns.

It remains to be seen how exactly implementation of the PMTA process will impact access to e-cigarettes. However, it’s likely that only large, well-funded manufacturers will be able to jump through the regulatory hurdles needed to obtain authorization for their products, which will in turn limit access, at least to some extent (as many small and mid-size companies who can’t jump through the hurdles will be forced to withdraw their products from the market). Also, we may see FDA use the PMTA process to eliminate access to certain types of e-cigarette products with broad youth appeal (e.g., fruity and candy-like flavors), limit the claims manufacturers can make about these products, require additional warnings, and/or place restrictions on distribution.

There have also been efforts to pass federal legislation aimed at restricting youth access to e-cigarettes. For example, in May 2019, Senator Mitch McConnell introduced a bill (the Tobacco-Free Youth Act) that would set a minimum tobacco purchasing age of 21 (which would apply to all tobacco products, including e-cigarettes). This seems to demonstrate the perceived importance of the youth access issue given that McConnell represents Kentucky, a major tobacco-growing state.

On the state and local levels, there have been a wide range of efforts aimed at restricting access to e-cigarettes, from increasing the minimum purchase age for e-cigarettes to 21, to taxes, to outright bans on these products. Below are some examples of these efforts:

San Francisco: In June 2019, an ordinance was passed (and later signed by the mayor) that will prohibit businesses in the city from selling e-cigarettes that have not received FDA marketing authorization (which none have yet). The ordinance will also ban all e-cigarettes that have not received FDA marketing authorization from being sold and distributed to consumers in the city (ordinance scheduled to take effect in early 2020).

Vermont: As of July 2019, state law prohibits anyone from causing e-cigarettes or substances containing nicotine (or intended for use with e-cigarettes) that are ordered or bought by mail, phone, or over the Internet to be shipped to anyone in Vermont other than a licensed wholesale dealer or retailer; a 92% tax on e-cigarettes will also go into effect.

Minnesota: As of August 2019, use of e-cigarettes in most indoor spaces is banned.

Beverly Hills: As of January 2021, an ordinance will take effect that prohibits gas stations, pharmacies, and convenience stores from selling tobacco products, including e-cigarettes.

Preventing youth use of e-cigarettes while maintaining availability of these products for current adult cigarette smokers is a complicated charge for legislators and regulators. While it will take some time to evaluate the impact of recent (and soon-to-be implemented) federal and state efforts, as next steps are considered, the need for balance should be kept at the forefront.

]]>https://www.healthlawadvisor.com/2019/08/14/whats-new-in-e-cigarette-regulation/feed/0Up in Smoke: The Countdown on Vape Enforcement Discretion Beginshttps://www.healthlawadvisor.com/2019/08/13/up-in-smoke-the-countdown-on-vape-enforcement-discretion-begins/
https://www.healthlawadvisor.com/2019/08/13/up-in-smoke-the-countdown-on-vape-enforcement-discretion-begins/#respondTue, 13 Aug 2019 15:02:00 +0000https://www.healthlawadvisor.com/?p=2960Continue Reading…]]>On July 11, 2019, a Federal judge for the U.S. District Court for Maryland ruled that manufacturers and importers of products such as e-cigarettes and other electronic nicotine delivery systems (“ENDS”) have ten months to submit applications for marketing to the U.S. Food and Drug Administration (“FDA”). The ten-month deadline is applicable to new tobacco products on the market as of the August 8, 2016 deeming rule that extended FDA’s regulatory jurisdiction to include all tobacco products. Accordingly, manufacturers of e-cigarettes now have until May 2020 to submit applications for market approval in order to continue selling their products.

E-cigarette manufacturers have thus far been able to sell products without FDA approval. In 2016, FDA announced its deeming rule that extended its regulatory jurisdiction over these products. Initially, FDA established a 2022 deadline for existing companies to submit applications for FDA approval. FDA requested in the application information about why the applicant companies should be permitted to keep selling these products. FDA decreased the deadline by one year, to 2021, after numerous studies found a sharp increase in the number of teenagers vaping. Unsatisfied with the one year difference, anti-tobacco groups filed a lawsuit[1] against FDA claiming the agency’s lack of urgency threatened public health. During the course of this lawsuit, FDA proposed the ten-month deadline for application submissions and a one-year deadline for approval. The judge noted that the four-month submission deadline for which the plaintiffs advocated was less reasonable and provided less time for applicants to present sufficient information to FDA. The judge’s ruling removed any agency discretion in regards to these deadlines.

In a response to the court order, Acting Commissioner of FDA Norman E. “Ned” Sharpless stated that “FDA stands ready to accelerate the review of e-cigarettes and other new tobacco products. . . .” and “remain[s] committed to tackling the epidemic of youth vaping using all available regulatory tools at our disposal.” Despite the impending deadline, the judge acknowledged that these companies “have large purses and the resources to complete promptly the applications that they have had before them for years.” However, in a brief filed last month FDA noted that by the end of April 2019 it had received over 400 premarket applications, ninety-nine percent of which did not meet the basic requirements. Clearly, it will require more than simply “large purses” to get these products approved.

Companies can look to FDA’s final guidance published in June 2019 for premarket tobacco product applications (“PMTAs”) for ENDS, which include, e-cigarettes, vape pens, and e-liquids. According to Commissioner Sharpless, the guidance provides companies seeking to market e-cigarette and ENDS products with “recommendations to consider as they prepare a premarket tobacco product application to help the FDA evaluate the public health benefits and harms of a product.” The guidance contains, among other things, the following components: (1) Background regarding FDA’s regulation of ENDS; (2) Products to which the Guidance applies; (3) General procedures for ENDS PMTA review; and (4) Content required in an ENDS PMTA and recommendations for demonstrating appropriateness for the protection of the public health (“APPH”).

ENDS are regulated under the federal Food, Drug, and Cosmetic Act (“FD&C Act” or the “Act”). Under section 910 of this Act, companies and/or persons wanting to market a new[2] tobacco product are required to follow the 905(j) pathway and submit either (1) a report to obtain a substantial equivalence determination or (2) a report notifying FDA of the product’s exemption under the FD&C Act. If the new product is not found to be substantially equivalent to an appropriately identified predicate product, companies must then submit a PMTA and seek a marketing order before marketing the product.

Applicable Products and When a PMTA Is Required

The Guidance applies to three subcategories of ENDS products: e-cigarettes, e-liquids, and “ENDS products that package e-liquids and e-cigarettes together” when they are sold or distributed for consumer use. For example, an e-liquid in a sealed and final package to be sold or distributed for consumer use would fall under FDA’s enforcement scope and be subject to the PMTA requirements.

ENDS PMTA Review

After the company submits its ENDS PMTA, FDA will conduct a preliminary review to determine whether the application appears to be complete on its face.[3] If initially accepted, FDA will then process a filing review, where it determines whether the ENDS PMTA is sufficiently complete to be filed and warrant a substantive review. Under the FD&C Act, once the FDA receives a complete ENDS PMTA and is filed, FDA has a 180-day period to conduct its substantive review and approve or deny the ENDS PMTA. During this substantive review, FDA may request clarification of deficiencies or additional information to supplement the ENDS PMTA.[4] FDA may also inspect manufacturing, clinical research, and/or nonclinical research sites to assess the accuracy and validity of information provided in the ENDS PMTA and confirm that the product and manufacturing process meets applicable standards. In the Guidance, FDA stated that it intends to issue regulations that will contain requirements for tobacco product manufacturing practices.

Contents of an ENDS PMTA

A complete ENDS PMTA must contain the required information under section 910(b)(1) of the Act. In the Guidance, FDA provides a recommended organization of this information, which should have, at a minimum: (1) general information with a cover letter that details any prior FDA submissions for the new product; (2) a table of contents; (3) “Descriptive Information” that describes major aspects of the new product, including an overview of its formulation and design, the nicotine strength, instructions for its use, any restrictions on sale and distribution that would support a showing that its marketing would be APPH, and specific e-cigarette and e-liquid recommendations like battery capacity/wattage and package quantity/type; (4) product samples; (5) proposed labeling that would minimize risk associated with product use (e.g., an e-cigarette’s battery failure warning based on storage conditions); (6) an environmental assessment[5]; and (7) detailed scientific studies and analyses of research findings.

FDA recommended that companies make sure to provide information on how to minimize risks associated with ENDS batteries and to address the likelihood of use and misuse leading to overheating, fire, and explosion. FDA also appeared especially concerned with these ENDS products’ appeal to youth and young adults (e.g., certain e-liquid flavors being more desirable to young adults). In fact, in FDA’s press release for the Guidance, FDA assured it would “explore clear and meaningful measures to make tobacco products less toxic, appealing and addictive with an intense focus on youth.” Recently, FDA appears to be adhering to this pledge with its first launch of youth e-cigarette advertisements.

Commissioner Sharpless encouraged companies to “use this valuable document now as a guide to submit applications,” especially since there are no authorized e-cigarettes on the market.

[2] FDA defines a “new” tobacco product as one that “was not commercially marketed in the United States as of (i.e., on) February 15, 2007, or any modified tobacco product that was commercially marketed after February 15, 2007.”

[3] FDA’s criteria for acceptance of a premarket submission for tobacco can be found in 21 C.F.R. 1105.10.

[4] As a note, FDA stated that “ENDS product[s] with a differing flavoring variant and/or nicotine strength” are considered different products and therefore must clearly indicate which information pertains to which product when submitting the PMTA for the group of products.

]]>https://www.healthlawadvisor.com/2019/08/13/up-in-smoke-the-countdown-on-vape-enforcement-discretion-begins/feed/0FDA Hosts Long-Awaited Cannabis Public Hearinghttps://www.healthlawadvisor.com/2019/06/04/fda-hosts-long-awaited-cannabis-public-hearing/
https://www.healthlawadvisor.com/2019/06/04/fda-hosts-long-awaited-cannabis-public-hearing/#respondTue, 04 Jun 2019 20:10:01 +0000https://www.healthlawadvisor.com/?p=2943Continue Reading…]]>On May 31, 2019, the U.S. Food and Drug Administration (“FDA”) hosted its much-anticipated public hearing titled “Scientific Data and Information about Products Containing Cannabis or Cannabis-Derived Compounds” (discussed in our prior blog post). The day-long hearing presented an opportunity for FDA panel members to engage directly with stakeholders on the regulatory future of cannabis or cannabis-derived products within the scope of FDA’s jurisdiction.

Acting FDA Commissioner Ned Sharpless, M.D., kicked off discussions, reminding the panel and stakeholders alike that it is “critical that we do all we can to support science to develop new drugs from cannabis.” Commissioner Sharpless emphasized that some uncertainty remains regarding the safety of widespread cannabis use, a sentiment echoed by stakeholders throughout the day.

Panel members included Amy Abernathy, FDA’s Principal Deputy Commissioner, and representatives from the Office of Foods and Veterinary Medicine and the Center for Drug Evaluation and Research. The panel heard from a diverse group of presenters, including members of academia, agriculture-focused groups, consumers, health care professionals, manufacturers of a variety of ingestible and topical cannabis or cannabis-related products, patients, retailers, and distributors, each offering various viewpoints on the safety, availability, and purity of cannabis products. Many presenters urged FDA to work quickly to develop and implement a regulatory framework, arguing that a protracted rulemaking process would unnecessarily delay the availability of helpful products. Overall, the stakeholders emphasized the need for a comprehensive regulatory framework that both protects consumers and eliminates current obstacles to the development of cannabis products. We provide a breakdown of key stakeholder and FDA perspectives below.

Expanded Research Initiatives

Representatives from academia and the health professional community advocated for lifting restrictions that currently apply to conduct of cannabis research because it is a Schedule I controlled substance, which means research must be approved by multiple federal and state agencies. They argued that, without the expanded ability to conduct research on cannabis products, the available data on the safety or quality of such products will be limited and it will be difficult to create appropriate quality control standards. Many speakers noted the need for more information about drug-drug interactions between cannabis products and other medications. Still others identified the need for research on dosing, as well as whether the route of cannabis administration impacts the safety of such products. Skeptics stressed that cannabis product use and dosage is difficult to figure out on an individual patient scale, so widespread public use could prove too dangerous without data to support safety and quality.

Labeling and Marketing Restrictions

Consumers, providers, and members of academia raised significant concern about the adequacy and accuracy of the information disclosed by manufacturers and retailers of cannabis products. They argued that the current lack of a uniform regulatory framework and FDA oversight has led to poor quality cannabis products that put consumers in danger. Multiple presenters cited data showing discrepancies between product labeling and content. For example, one speaker reported that a cannabidiol (“CBD”) product labeled as “THC-free” actually contained tetrahydrocannabinol (“THC”) and also contained a different concentration of CBD than was stated on the label. A number of speakers discussing this topic argued that misrepresentations in labeling constituted “abuse” by the industry that must be addressed on a federal level.

Uniform Guidance for States on Legal Pathways to Market

Stakeholders at the hearing included those representing various state governments. These representatives discussed the increasing challenges for states to both meet economic needs and remain compliant with federal regulations as the consumer demand and market availability for these products grow. These representatives called for clarity and uniformity from FDA in a variety of contexts, including more guidance on which products are subject to regulation as Schedule I controlled substances in collaboration with the federal Drug Enforcement Agency and which are regulated by FDA alone, pathways to market for CBD dietary supplements and food products, and regulations for extraction and production of cannabis-related compounds. Some of the state representatives explained that such clarification from FDA would be helpful for their own legislatures that are working to develop state regulatory schemes for cannabis or cannabis-related products.

Some retailers and manufacturers identified certain cannabis-related compounds, which do not contain CBD or THC, as “low hanging fruit” for which FDA can clear a pathway to market. Examples included terpenes, a large group of organic compounds responsible for the taste and flavor of cannabis that are also found in other plants and fruits, as well as cannabis-free hemp products. Retailers and manufacturers urged FDA to acknowledge such products to be generally recognized as safe (“GRAS”) as a first step in its regulatory scheme.

Adverse Event Reporting

Many presenters argued that CBD has been verified as safe, non-habit forming, and non-toxic. However, others disputed these claims, arguing that there is not enough evidence to demonstrate that CBD is not addictive or non-toxic, citing to research findings that suggest potential complications involving withdrawal symptoms and impaired liver function.

The panel questioned whether the industry has observed a lack of incentive by pharmaceutical manufacturers to develop drug products containing cannabis or cannabis-derived compounds because of CBD’s broad availability. Most stakeholders recognized a need to distinguish between FDA-approved cannabis drug products necessary to treat serious medical conditions, and more widely available cannabis-derived dietary supplement or food products. As one stakeholder put it, FDA needs to “treat medicine as medicine,” implying that therapeutic cannabis products should be regulated consistent with FDA’s existing drug regulatory framework. Finally, throughout the hearing, panel members seemed keen on receiving detailed clinical study or testing data in comment form from companies that have already conducted this research.

Next Steps

FDA representatives did not give any indication of what, if any, regulatory changes the agency was considering, how the feedback from the hearing would be incorporated into the agency’s decision-making, or the timing of any proposed regulatory changes. Stakeholders with an interest in developing, marketing, distributing, or purchasing consumer-focused CBD products—as well as in developing other hemp-derived cannabinoid compounds for the consumer market—can still submit comments for FDA’s consideration via regulations.gov by July 2, 2019. Many stakeholders during the hearing requested an extension of this deadline, but it is unclear whether FDA will grant this request.

Lauren Petrin, a 2019 Summer Associate (not admitted to the practice of law) in the firm’s Washington, DC office, contributed significantly to the preparation of this post.

]]>https://www.healthlawadvisor.com/2019/06/04/fda-hosts-long-awaited-cannabis-public-hearing/feed/0The Role of Patient Preference in Medical Device Evaluationhttps://www.healthlawadvisor.com/2019/05/23/the-role-of-patient-preference-in-medical-device-evaluation/
https://www.healthlawadvisor.com/2019/05/23/the-role-of-patient-preference-in-medical-device-evaluation/#respondThu, 23 May 2019 16:28:52 +0000https://www.healthlawadvisor.com/?p=2941Continue Reading…]]>When we think about the top players in the medical device development space, we often see device company sponsors, clinicians, scientists, and FDA regulators as the ones driving the process. But what about the patient perspective? Does that get factored in?

On May 3, 2019, FDA established a docket to collect public input on a proposed list of patient preference-sensitive areas for medical device review, and posed certain related questions (comments are due July 2, 2019). By identifying these key areas (which it committed to as part of the reauthorization of the Medical Device User Fee Amendments of 2017 (MDUFA IV)), FDA hopes to advance patient input, which can help inform and improve regulatory decision-making. FDA has grouped these proposed patient-preference sensitive areas (full list available here) into the following four umbrella categories:

Stepping back for a moment, though, it’s important to understand what exactly patient preference information is and how FDA has addressed patient preference information to date.

What is Patient Preference Information (PPI)?

FDA defines PPI as “qualitative or quantitative assessments of the relative desirability or acceptability to patients of specified alternatives or choices among outcomes or other attributes that differ among alternative health interventions.” Put simply, PPI can help inform what’s important to patients and can be useful in evaluating a device’s benefit-risk profile, particularly when treatment options are “preference sensitive” (i.e., multiple treatments exist and no option is clearly superior or the evidence supporting one option over the others is uncertain).

What Efforts has FDA Previously Undertaken to Advance the Patient Perspective?

Since 2013, FDA has taken several actionable steps to recognize the voice of patients, including the following:

2013 – FDA launched the Patient Preference Initiative, and hosted a public workshop to discuss ways to incorporate patient preferences on device benefit-risk trade-offs into Center for Devices and Radiological Health (“CDRH”) decision-making, and advance the science of measuring patient and provider treatment preferences.

2015 – FDA announced the first Patient Engagement Advisory Committee (PEAC), supported by CDRH, which provides advice to the FDA Commissioner on complex issues relating to devices and their use by patients, with the goal of increasing integration of patient perspectives into the regulatory process.

2017 – FDA co-hosted a workshop presenting current progress on incorporating PPI into medical product reviews and how PPI can be collected and presented (among other topics).

As patients become increasingly interested and engaged in their health care decisions, it makes a lot of sense for their perspectives to be considered by regulators who are evaluating the benefits and risks of proposed products. Of course, however, it is important that patient preference information is accurately measured and appropriately weighted in the decision-making process. To that end, FDA advises sponsors that are considering patient preference studies to consult with the Agency early on in the process.

]]>https://www.healthlawadvisor.com/2019/05/23/the-role-of-patient-preference-in-medical-device-evaluation/feed/0FDA Declines to Ban Breast Implants, Will Require Full MDR Reporting by Manufacturershttps://www.healthlawadvisor.com/2019/05/16/fda-declines-to-ban-breast-implants-will-require-full-mdr-reporting-by-manufacturers/
https://www.healthlawadvisor.com/2019/05/16/fda-declines-to-ban-breast-implants-will-require-full-mdr-reporting-by-manufacturers/#respondThu, 16 May 2019 13:40:48 +0000https://www.healthlawadvisor.com/?p=2937Continue Reading…]]>Following a two-day meeting by a Food and Drug Administration (“FDA”) advisory committee on breast implant safety earlier this year, FDA on May 2, 2019, released a statement announcing that no breast implant models will be banned from the U.S. market at this time. Also described in the statement are a number of measures the agency is undertaking in order to assist women in making more informed decisions regarding breast implants.

The March 26, 2019, meeting of the General and Plastic Surgery Devices Panel was convened to discuss issues and concerns related to the benefit-risk profile of breast implants, including a potential link between textured breast implants and breast-implant associated anaplastic large cell lymphoma (“BIA-ALCL”). The panel heard testimony from nearly 40 member surgeons of the American Society of Plastic Surgeons as well as from a number of women who stated that they suffered adverse health consequences after receiving breast implants. The panel recommended that health care providers implement stronger informed consent practices for breast implant surgeries, including disclosure of information regarding the signs and symptoms of breast implant illness (“BII”) and BIA-ALCL as well as the increased risk of BIA-ALCL with textured implants.

According to the May 2 statement, which was jointly issued by FDA Principal Deputy Commissioner Amy Abernethy and Center for Devices and Radiological Health Director Jeff Shuren, FDA concluded after reviewing available data and information that textured breast implants do not meet the legal standard for imposing a ban under the Food, Drug, and Cosmetic Act. The statement points out that while “the majority of women who develop BIA-ALCL have had textured implants, there are known cases in women with smooth-surface breast implants and many reports do not include the surface texture of the implant at the time of diagnosis.”

The statement also announced a change of policy with respect to adverse event reporting. Manufacturers of breast implants will no longer be permitted to submit summary reports of adverse events and instead will be required to file individual medical device reports (“MDRs”) that will be publicly available in the Manufacturer and User Facility Device Experience (“MAUDE”) database. FDA will also make the previously submitted summary reports public in the coming weeks. Additionally, FDA will work with primary stakeholders on developing the content and format of possible boxed warnings or patient checklists for breast implants in order to communicate significant health concerns and risks associated with breast implants.

According to the statement, FDA also is undertaking new efforts to improve the characterization of, and risk factors for, BII and to increase information available to women to enable more informed decision-making about “whether to obtain breast implants or to remove existing breast implants in an effort to reverse systemic symptoms.” The agency also plans to examine whether device materials may cause immune or inflammatory reactions among certain predisposed individuals, and may require disclosure of breast implant ingredient information to be included in product labeling.

Shortly before the March 26 meeting, FDA sent warning letters to two manufacturers of breast implants for failing to adequately comply with post-market commitments to study the long-term safety of their products. These actions, coupled with FDA’s recent statement, signal that breast implant safety is a high-priority issue for the agency. Manufacturers, providers, payors, and other stakeholders should carefully evaluate the potential impact of FDA’s announced initiatives on their activities.

]]>https://www.healthlawadvisor.com/2019/05/16/fda-declines-to-ban-breast-implants-will-require-full-mdr-reporting-by-manufacturers/feed/0FDA Announces New Proposed Rule to Enhance Mammography Serviceshttps://www.healthlawadvisor.com/2019/04/03/fda-announces-new-proposed-rule-to-enhance-mammography-services/
https://www.healthlawadvisor.com/2019/04/03/fda-announces-new-proposed-rule-to-enhance-mammography-services/#respondWed, 03 Apr 2019 18:38:28 +0000https://www.healthlawadvisor.com/?p=2904Continue Reading…]]>On March 27, 2019, the FDA announced that it would be proposing new amendments to key regulations regarding mammography facilities that would require these entities “to tell women more about how dense breast tissue can affect their health and increase their cancer risk.” The proposed changes to mammography facility regulations would be the first issued in more than 20 years. The FDA believes the change will “expand the information mammography facilities must provide to patients and health care professionals, allowing for more informed medical decision-making.” In addition, FDA is proposing to modernize quality standards by, for example, expressly authorizing FDA communications with patients and practitioners in the event of quality issues, requiring use of FDA-approved or -cleared digital accessories, and strengthening recordkeeping requirements. These changes not only enhance regulatory requirements, but likely foreshadow increasing enforcement and communications from FDA with regard to mammography services.

As a general rule, it is a well settled rule of law that FDA does not regulate the practice of medicine, but mammography services are a notable exception. Congress provided the FDA with regulatory oversight of mammography facilities in 1992 following passage of the Mammography Quality Standards Act (MQSA). The MQSA entrusts FDA with facility accreditation, annual inspections, certification, and enforcement of standards to assist in ensuring such facilities provide quality care. FDA Commissioner Scott Gottlieb remarked that the new rule proposal would “modernize our oversight of mammography services, by capitalizing on a number of important advances in mammography, like the increased use of 3-D digital screening tools and the need for more uniform breast density reporting.”

Under the proposed rule, mammography providers would be required to tell women whether they have dense breast tissue, which may increase cancer risk and mask tumors, making cancer detection more challenging. Women with dense tissue are often advised to seek other screening tests along with mammograms, such as M.R.I. scans or ultrasound, but in many states this is left to the discretion of providers. (Currently, there are roughly 36 states already requiring that female patients be given information about breast density). The new rule proposes specific language that would be implemented nationwide to explain breast density, note that some women may need additional imaging tests and recommend patients consult their physicians regarding their results. The FDA language would set a minimal standard, and will not preempt states from imposing additional requirements regarding disclosures.

The content of communications beyond basic diagnosis have been raised as a concern under current state law disclosure standards. Some within the medical profession have argued that disclosure laws could provide women with information that does not necessarily reflect their condition, and could lead to a demand for expensive, unnecessary tests. Further, some physicians have also suggested that state-mandated letters may be too complex for patients to understand. For instance, the Journal of the American Medical Association (JAMA) published a study analyzing notification letters sent out in over 20 states and found that “many use such complex language that patients need a college degree to understand them.” Acknowledging the pushback, Commissioner Gottlieb stated that women had a right to receive such information regarding their health in order to make an informed decision about next steps.

Moving forward, entities and medical professionals should be mindful of these regulations when providing mammography services to female patients. It will be important to exercise best medical judgment when examining mammogram results as dense breast tissue may represent a significant confounder when assessing breast cancer risk. Communications on these topics could face additional scrutiny as medical practitioners try to balance obligations in regulations with general principles about informing patients about their condition in an understandable manner. In addition, there is potential that changes could drive an increase the use of additional diagnostic testing. Thus, there is some uncertainty as to whether there should be a push for enhanced screening.

]]>https://www.healthlawadvisor.com/2019/04/03/fda-announces-new-proposed-rule-to-enhance-mammography-services/feed/0FDA Commissioner Gottlieb Says Agency Will Not Tolerate Deceptive Marketing of CBD Products; Issues Warning Lettershttps://www.healthlawadvisor.com/2019/04/03/fda-commissioner-gottlieb-says-agency-will-not-tolerate-deceptive-marketing-of-cbd-products-issues-warning-letters/
https://www.healthlawadvisor.com/2019/04/03/fda-commissioner-gottlieb-says-agency-will-not-tolerate-deceptive-marketing-of-cbd-products-issues-warning-letters/#respondWed, 03 Apr 2019 17:58:08 +0000https://www.healthlawadvisor.com/?p=2901Continue Reading…]]>On April 2, 2019, FDA issued a press release featuring a statement from FDA Commissioner Scott Gottlieb announcing the Agency’s latest enforcement actions taken against companies engaging in unlawful marketing of cannabidiol (CBD) products. Coming just days before Gottlieb’s anticipated departure from the Agency, this news otherwise is unsurprising given recent events on the federal and state level. In a December 2018 press release issued on the heels of the Farm Bill’s passage, FDA forecast its intention to step up enforcement against CBD products, and earlier this year state and local governments initiated seizures of CBD products from store shelves. For manufacturers, retailers, and consumers, the takeaway from these recent statements and actions is that it remains unlawful under the Federal Food Drug and Cosmetic (FD&C) Act to market conventional foods or dietary supplements containing CBD.

The April 2, 2019 press release announces the issuance of three Warning Letters to companies marketing CBD products using “egregious and unfounded claims that are aimed at vulnerable populations.” Notably, the Warning Letters were issued jointly by FDA and the Federal Trade Commission, which has authority to protect consumers from unfair trade practices, including false or misleading advertising claims. As examples of unlawful claims, the Warning Letters cite assertions that CBD products stop growth of cancer cells, slow the progression of Alzheimer’s, and reduce withdrawal symptoms in individuals with substance use disorders. While FDA’s position is that the inclusion of CBD as an ingredient in conventional foods and dietary supplements is per se unlawful, the Agency’s focus on companies making cure or treatment claims for serious diseases and conditions is consistent with the December 2018 statement that the Agency would prioritize enforcement against products the Agency believes put consumers at risk.

The press release also sets a date for the previously promised public hearing on the future of CBD product regulation. The hearing, which is scheduled for May 31, 2019, will provide a platform for interested parties to “share their experiences and challenges” under the current regulatory environment. A newly-created internal Agency working group will be tasked with reviewing and analyzing stakeholder feedback and exploring potential regulatory pathways for CBD products. FDA seeks stakeholder feedback on issues including the levels of cannabis and cannabis-derived compounds that cause safety concerns; how the mode of delivery (e.g., ingestion, absorption, inhalation) affects the safety of, and exposure to, these compounds; and how cannabis and cannabis-derived compounds interact with other substances such as drug ingredients.

Stakeholders with an interest in developing, marketing, distributing, or purchasing consumer-focused CBD products—as well as in developing other hemp-derived cannabinoid compounds for the consumer market—can submit comments or a request to make an oral presentation at the hearing by May 10, 2019. Stakeholders can also submit comments for FDA’s consideration after the hearing via regulations.gov by July 2, 2019.

]]>https://www.healthlawadvisor.com/2019/04/03/fda-commissioner-gottlieb-says-agency-will-not-tolerate-deceptive-marketing-of-cbd-products-issues-warning-letters/feed/0Obscure FDA Device Reporting Exemptions Draw Patient and Provider Concernhttps://www.healthlawadvisor.com/2019/03/28/obscure-fda-device-reporting-exemptions-draw-patient-and-provider-concern/
https://www.healthlawadvisor.com/2019/03/28/obscure-fda-device-reporting-exemptions-draw-patient-and-provider-concern/#respondThu, 28 Mar 2019 19:55:00 +0000https://www.healthlawadvisor.com/?p=2899Continue Reading…]]>Many physicians rely on publicly available reports to assess the safety of the devices they use on patients, but in some cases, these reports aren’t painting the full picture. A recent Kaiser Health News (“KHN”) article raises serious questions about FDA’s practice of allowing a significant number of medical device injury and malfunction reports to stay out of the public eye.

Both mandatory and voluntary adverse event reports dating back to the 1990s are housed in FDA’s publicly-accessible Manufacturer and User Facility Device Experience Database (“MAUDE”), which is updated by the Agency monthly. However, according to FDA’s website, MAUDE may not include reports made according to “exemptions, variances, or alternative reporting requirements granted under 21 CFR 803.19.”

The KHN article examined the scope of such “hidden” reporting channels, which keep certain device injury and malfunction reports from ever seeing the light of day. In fact, according to KHN’s investigation, since 2016, more than one million device incidents have been able to bypass inclusion in the MAUDE database as a result of FDA’s “alternative summary reporting program.”

Under this program, which launched in 2000, device manufacturers have been able to seek an “alternative summary” reporting exemption, permitting them to send FDA an accounting of device injuries and malfunctions on a periodic basis (e.g., quarterly or annually) in lieu of fulfilling their standard public reporting obligations. Initially, only a few devices had been granted reporting exemptions, but today, about 100 devices, from surgical staplers to balloon pumps to mechanical breathing machines, are subject to exemptions. The internal Agency database tied to this program is not open to the public.

FDA has also granted other types of reporting exemptions. For example, pelvic mesh manufacturers have been granted a special “litigation complaint summary reporting” exemption. This allows them to submit a single “injury” report to FDA, but attached to that summary report may be a listing of hundreds of patient injury reports (based on lawsuit allegations). For someone reviewing pelvic mesh injuries in MAUDE, this would look like a single injury, with the underlying detail (and sometimes voluminous) patient injury reports tied to the summary report only being accessible through a Freedom of Information Act request.

According to FDA, for certain devices, alternative summary reporting helps eliminate redundant paperwork for the Agency. But for physicians and patients, many of whom have no awareness of FDA’s “alternative” reporting mechanisms (and thus perceive the publicly available reports as the full universe of available safety information), the lack of transparency is troubling. Where patient care decisions are in the balance, administrative efficiency should not trump the need for full public access to device injury and malfunction information. At the very least, FDA should be completely transparent about the types of reporting exemptions that have been granted, and the specific devices that are subject to exemptions.